Effective pilot and/or exploratory studies are key steps towards the development of successful, externally- funded research proposals, particularly for early-stage investigators or those entering into a new field of study. The WF OAIC Pilot and Exploratory Studies Core (PESC) proposes to continue our coordinated, multi- faceted group effort to promote pilots and exploratory studies that address the WF OAIC mission, through a process that incorporates continued innovation. Our overall goal is to develop key information needed for the design of definitive, externally funded, translational research studies that will advance our knowledge and understanding of pathways influencing physical function, all in support of WF OAIC theme: Integrating pathways affecting physical function for new approaches to disability treatment and prevention. Our goal will be achieved through the following Specific Aims: 1) To identify and promote promising key areas of research becoming ripe for investment; 2) To identify and recruit talented key investigators from complementary fields to participate in OIAC-relevant research; 3) To solicit multiple competitive research proposals in each cycle, and conduct internal and external peer review to identify and select the best science; 4) To actively interact with and mentor investigative teams, to maximize the quality of research proposals and projects and help insure their success; 5) To work closely with the other WF OAIC cores to advance pilot projects and mentor early-stage investigators, advancing their development as successful translational scientists; and 6) To continue to refine and optimize approaches to OAIC PESC procedures. Over the latest cycle, the PESC developed and managed a strong portfolio of successful pilot and exploratory studies in pursuit of the WFU OAIC theme. These have encompassed relatively basic science studies regarding key biomolecular pathways involved in physical function, all the way to development and implementation of new approaches to characterize and improve physical function in the clinic. The PESC has continued to have remarkable productivity, leading to 20 externally funded grants totaling $24 million, a 114% increase over the last cycle. This increase is even more significant given challenging funding environment. Under the continuing leadership of Drs. Kitzman and Register, the WF PESC will support 4 innovative pilot projects in the first year of the upcoming cycle, each led by a talented early-career investigator. The projects advance different stages of translational science, from discovery to implementation. Two studies incorporate basic and geroscience approaches to 1) senescence and 2) the microbiome into ongoing human studies. Two studies will test interventions in the clinical setting to use 3) exercise or 4) mindfulness approaches to alleviate pain. All are aligned with the OAIC theme of promoting independence through discovery and translation.